title: Polymorphisms of glucose-regulated protein 78 and risk of colorectal cancer: a case-control study in southwest China.
abstract: Glucose-regulated protein 78 (GRP78), an endoplasmic reticulum chaperone, up-regulation serves as an efficient mechanism to promote malignant transformation of colorectal cancer (CRC) and protect CRC cells against apoptosis. Recently, the analysis of GRP78 polymorphisms has already determined that GRP78 rs391957 polymorphism could predict clinical outcome in CRC patients. Thus, we tested whether GRP78 polymorphisms are related to the risk of CRC. In this study, we detected two GRP78 polymorphisms (rs391957 (C>T) and rs430397 (G>A)) in 414 CRC cases and 502 hospital-based cancer-free healthy controls in Southwest China using a polymerase chain reaction-restriction fragment length polymorphism technique. Compared with the CC genotype, carriers of CT and TT genotypes of rs391957 polymorphism had higher risks of CRC (odds ratio (OR) = 1.39, 95% confidence interval (CI) = 1.06-1.83 for CT genotype and OR = 2.10, 95% CI = 1.06-4.14 for TT genotype, respectively). In CRC cases, the variant T allele was significantly associated with tumor invasion stage (P = 0.030), but not with status of lymph nodes metastasis (P = 0.052). Compared with the GG genotype, carriers of GA and AA genotypes of rs430397 polymorphism had higher risks of CRC (OR = 1.63, 95% CI = 1.23-2.15 for GA genotype and OR = 2.92, 95% CI = 1.23-6.94 for AA genotype, respectively). The rs430397 polymorphism was not associated with the clinicopathological characteristics of CRC. These data provide the first evidence that GRP78 rs391957 and rs430397 polymorphisms could serve as markers to predict the risk of CRC.
authors.affiliation: Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhang
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.forename: Mojin
authors.initials: M
authors.lastname: Wang
authors.forename: Cun
authors.initials: C
authors.lastname: Wang
authors.forename: Zongguang
authors.initials: Z
authors.lastname: Zhou
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Sun
mesh_terms: D000368:Aged; D044466:Asian People; D016022:Case-Control Studies; D002681:China; D015179:Colorectal Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins